Kinetic insights into ϵ-caprolactone synthesis: Improvement of an enzymatic cascade reaction

Biotechnol Bioeng. 2017 Jun;114(6):1215-1221. doi: 10.1002/bit.26258. Epub 2017 Mar 14.

Abstract

A computational approach for the simulation and prediction of a linear three-step enzymatic cascade for the synthesis of ϵ-caprolactone (ECL) coupling an alcohol dehydrogenase (ADH), a cyclohexanone monooxygenase (CHMO), and a lipase for the subsequent hydrolysis of ECL to 6-hydroxyhexanoic acid (6-HHA). A kinetic model was developed with an accuracy of prediction for a fed-batch mode of 37% for substrate cyclohexanol (CHL), 90% for ECL, and >99% for the final product 6-HHA. Due to a severe inhibition of the CHMO by CHL, a batch synthesis was shown to be less efficient than a fed-batch approach. In the fed-batch synthesis, full conversion of 100 mM CHL was 28% faster with an analytical yield of 98% compared to 49% in case of the batch synthesis. The lipase-catalyzed hydrolysis of ECL to 6-HHA circumvents the inhibition of the CHMO by ECL enabling a 24% higher product concentration of 6-HHA compared to ECL in case of the fed-batch synthesis without lipase. Biotechnol. Bioeng. 2017;114: 1215-1221. © 2017 Wiley Periodicals, Inc.

Keywords: computer simulation; enzymatic cascades; oxidoreductases; reaction engineering; ϵ-caprolactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / chemistry*
  • Caproates / chemical synthesis*
  • Enzyme Activation
  • Hydrolysis
  • Kinetics
  • Lactones / chemical synthesis*
  • Lipase / chemistry*
  • Multienzyme Complexes / chemistry
  • Oxygenases / chemistry*
  • Sorbic Acid / analogs & derivatives
  • Sorbic Acid / chemistry
  • Substrate Specificity

Substances

  • Caproates
  • Lactones
  • Multienzyme Complexes
  • caprolactone
  • 6-hydroxy-2,4-hexadienoic acid
  • Alcohol Dehydrogenase
  • Oxygenases
  • cyclohexanone oxygenase
  • Lipase
  • Sorbic Acid